RT Journal Article
SR Electronic
T1 Induction of Apoptosis by Sphingosine, Sphinganine, and C<sub>2</sub>-Ceramide in Human Colon Cancer Cells, but not by C<sub>2</sub>-Dihydroceramide
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2881
OP 2884
VO 30
IS 7
A1 AHN, EUN HYUN
A1 SCHROEDER, JOSEPH J.
YR 2010
UL http://ar.iiarjournals.org/content/30/7/2881.abstract
AB Complex dietary sphingolipids such as sphingomyelin and glycosphingolipids have been reported to inhibit the development of colon cancer. This protective role may be the result of the conversion of complex sphingolipids to bioactive metabolites including sphingoid bases (sphingosine and sphinganine) and ceramide, which inhibit proliferation and stimulate apoptosis. In the current study, we evaluated the significance of the 4,5-trans double bond by comparing the effects of sphingosine and the cell permeable short-chain ceramide analog C2-ceramide to those of sphinganine and C2-dihydroceramide, which lack this structural feature. The effects of the sphingoid bases, C2-ceramide, and C2-dihydroceramide on apoptosis were determined by detecting 200-bp DNA ladders or hypo-diploid areas (sub-G0/G1), indicative of apoptosis, in HCT-116 human colon cancer cells. In addition, the effects of the sphingoid bases at an apoptotic concentration for 12 hours on cell cycle distribution were determined by flow cytometry. The results indicated that the sphingoid bases and C2-ceramide induced apoptosis, whereas C2-dihydroceramide had no effects. Sphingoid bases arrested the cell cycle at the G2/M phase. The present study provides evidence that the 4,5-trans double bond is necessary for the apoptotic effect of C2-ceramide, but not for that of sphingoid bases.